The PI proposes to design and synthesize several new 3,4-dihydro-2(1H)-quinolones as potential anticonvulsant drug candidates, based upon the observed anticonvulsant activity of two lead compounds, which exhibit good anti- MES (active against electrically-induced seizures) and anti-PTZ (active against pentylenetetrazol-induced seizures) activities. In the Phase studies, the PI proposes to test the feasibility of enhancing, by appropriate structural manipulation and rational synthesis, the anticonvulsant activity of new 3-substituted and 3,3-disubstituted 3,4- dihydro-2(1H)-quinolones. He plans to utilize unique and convenient new synthetic methodology, based upon the generation and regioselective reaction of N,C3-dianions derived from 3,4-dihydro-2(1H)-quinolones, which he claims represents new chemical technology. PROPOSED COMMERCIAL APPLICATION: In light of the significant number of people affected by epilepsy as well as the limited number of approved therapeutic agents available for treatment, there is an urgent need to pursue the development of new generation antiepileptic drugs (AEDs) which exhibit greater efficacy against seizures, lower neurotoxicity and fewer deleterious side effects. As originally outlined in the proposal for this STTR Phase I project, we are currently preparing a number of derivatives of 3,4- dihydro-2(1H)-quinolone in order to evaluate their potential as anticonvulsant drug candidates. Biological screening of these compounds is expected to provide a clearer understanding of the structural requirements necessary for their anticonvulsant properties, as well as possible clues to their mechanism of action. This, in turn, will more sharply define our synthetic goals for Phase II investigations of this new class of potential AEDs. The synthetic methodology we have devised provides low-cost, ready access to these quinolone derivatives on any production scale, from mg to kg, making this technology amenable to commercial production. If these novel, structurally simple, and readily modified compounds prove to be efficacious, potential commercial applications would include patent considerations for the process and the drugs themselves, as well as their large-scale manufacture.